Porous matrix and method of its production

ABSTRACT

Low density fused fibrous ceramic composites are prepared from amorphous silica and/or alumina fibers with 2 to 12% boron nitride by weight of fibers, used as a fluxing agent to reduce the melting temperature of the fibers and allow the fibers to fuse at their intersections creating a three dimensional rigid matrix. The matrix is useful as a cell-culture substrate, as an implant material, and for chromatographic separation of blood cells.

FIELD OF THE INVENTION

The present invention relates to a low-density porous matrix, and to amethod of making the matrix.

BACKGROUND OF THE INVENTION

Porous biomaterials in use today are extractions from naturallyoccurring materials such as "coral" or artificially fabricated usingpolymers and hydroxyapatite formulated structures. These structures arenot optimized and heretofore, their porosity and densities may beensuboptimal for cell growth. Naturally occurring materials such as"coral" have low porosity and cannot guarantee a permeable open cellmatrix free from "cul-da-sac" type cavities.

They have limited bio-compatibility and have resulted in either apathological response from the body or failed to enhance multi-layercellular growth. Current biomaterials are difficult to shape and machineat the use site.

SUMMARY OF THE INVENTION

The invention includes, in one embodiment, a porous matrix composed offused silica, alumina, or silica and alumina fibers. The matrix ischaracterized by (a) a rigid, three-dimensionally continuous network ofopen, intercommunicating voids, (b) a density of between about 3.5 and5.5 pounds/ft3; and (c) a free volume of between about 90-98 volumepercent.

In one embodiment, the fibers have diameters between about 0.5 and 5 μm,fiber lengths between about 1-10 mm. In an alternative embodiment, thesilica fibers have about the same fiber lengths and fiber diametersbetween about 5 to 20 μm, giving relatively larger pores of voids in thematrix. Alternatively, the matrix may have a gradient of fiber diametersin one of the matrix dimensions, or a gradient of matrix density in onematrix dimension.

Also in a preferred embodiment, the matrix contains between 1-5 percentby weight silicon carbide particles.

For use as a matrix for cell culture, the matrix may have a lattice ofinternal channels through which liquid medium can be supplied tointernal regions of the matrix. In an alternative embodiment for use incell culture, the matrix may be constructed to include a series ofspaced, parallel plates.

For use as a body implantable material, for supporting tissue growth invivo, the matrix may be coated with a biocompatible material at itsouter surface. For use as a bioimplantable material for bone growth, thesilica fibers may be derivatized with a bone osteogenic factor.

For use in affinity chromatography, the silica fibers may be derivatizedwith molecules effective to bind ligand molecules passed through thematrix.

For use in a blood diagnostics assay in which a blood sample applied toone region of the matrix is chromatographically separated into bloodcells and cell-free serum, the matrix may further include a detectionregion at which a selected analyte in serum can be detected.

In another aspect, the invention includes a method of producing a rigidfused silica, alumina, or silica and alumina fiber matrix of the typedescribed above. The method includes forming a slurry composed of (i)silica, alumina, or silica and alumina fibers having selected fiberthicknesses in the size range between about 0.5 and 20 μm and fiberlengths between about 1 and 10 mm, at a fiber:liquid weight ratio ofbetween about 1:25 to 1:70, (ii) a viscosity agent effective to give theslurry a viscosity between about 1,000 and 25,000 centipoise, (iii)boron nitride particles, in an amount between about 2-12 percent byweight of the total fiber weight, and (iv) where the fibers includesilica fibers, a dispersing agent effective to enhance the dispersion ofthe silica fibers in the slurry,

The slurry is allowed to settle under conditions effective to produce afiber block having a selected fiber density between about 3.3 and 5.3pounds/ft³, and the block is then dried to form a rigid, substantiallydehydrated fiber block. This block is heated to a temperature of atleast about 2200° F. for a period sufficient to cause the silica fibersto form a fused-fiber matrix.

The slurry may be formed with fibers having a selected fiber thickness,in a selected size range between about 1-20 μm, to achieve a selectedpore size in the matrix. The slurry may also include silicon carbide inan amount between 1-5 percent of the total fiber weight.

The boron nitride is preferably present as 15 to 60 μm size particles,and the viscosity agent is preferably one, such as methyl cellulose,effective to enhance binding of boron nitride to the fibers.

The slurry may be allowed to settle under conditions that produce afiber density gradient in the direction of settling. Alternatively, informing a density or compositional matrix gradient, two or moredifferent slurries may be poured and allowed to settle successively. Foruse as a matrix for cell culture, the dehydrated block may be formed toinclude a lattice of linked strands of graphite or polymer which, duringthe heating step, vaporize to leave a lattice of interconnected channelsthrough which liquid medium can be circulated through the interior ofthe matrix.

In still another aspect, the invention includes a method offractionating blood into cell and serum components. The method includesplacing a blood sample at one end of an elongate strip of porous matrixof the type described above, and allowing the sample to migrate bycapillarity toward the other end of the strip, wherein migration of cellparticle components in the blood is retarded by the network fibers,producing a chromatographic separation of faster-migrating serum andslower-migrating cells.

Also contemplated by the invention is a fibrous matrix comprising aporous matrix composed of fused polymer fibers. The matrix ischaracterized, in dry form, by: (a) a rigid, three-dimensionallycontinuous network of open, intercommunicating voids, and (b) a freevolume of between about 90-98 volume percent, and silica and/or aluminafibers or particles attached to the polymer fibers.

These and other objects and features of the invention will become morefully apparent when the following detailed description of the inventionis read in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES

FIGS. 1A and 1B illustrate two embodiments of a fused-silica matrixconstructed in accordance with the invention, with portions cutaway toshow internal features of the first matrix;

FIGS. 2A-2D show scanning electron micrographs of the FIG. 1 matrixtaken at magnifications of 220 (2A), 1,000 (2B), 3,000 (2C), and 7,000(2D);

FIGS. 3A and 3B show a matrix having a continuous fiber-density gradient(FIG. 3A) and a discontinuous fiber-diameter gradient (FIG. 3B);

FIG. 4 is a plot showing percent mercury intrusion into matrices formedwith fiber diameters of 1.3 μm (dash-dot line), 3 μm (dotted line), 6 μm(dash-2-dot line), and a mixture of 1.3 and 3 μm (dashed line), as afunction of intrusion pressure;

FIGS. 5A and 5B are scanning electron micrographs of a matrixconstructed from different-density layers, taken at the interface regionbetween plates of different density, at 100× (4A) and 500× (4B)magnification;

FIG. 6 shows the distribution of boron nitride particles onrepresentative silica fibers in the green-state block;

FIGS. 7A-7C illustrate steps in compacting a silica-fiber slurry, inpreparing a green-state fiber block, in the method of the invention;

FIG. 8 is a flow diagram showing steps is forming a compressed slurryaccording to various embodiments of the method of the invention;

FIGS. 9A and 9B show a polymer-fiber matrix constructed in accordancewith another embodiment of the invention;

FIGS. 10A-10C illustrate three cell culture systems employing variousmatrix embodiments of the invention;

FIG. 11 shows a prosthetic device containing a matrix cap constructed inaccordance with the invention;

FIG. 12 shows an implantable cell matrix device constructed inaccordance with the invention; and

FIG. 13A and 13B illustrate the use of the invention for blood-sampleseparation in a diagnostic device.

DETAILED DESCRIPTION OF THE INVENTION

I. Fiber Matrix

FIGS. 1A and 1B illustrate two embodiments of a fused-fiber matrixconstructed in accordance with the invention. Each matrix is composed offused silica, alumina, or silica and alumina fibers, such as will bedescribed below with reference to FIGS. 2A-2D, and is characterized by(a) a rigid, three-dimensionally continuous network of open,intercommunicating voids, (b) a density of between about 3.5 and 5.5pounds/ft3; and (c) a free volume of between about 90-98 volume percent.Other ceramic fibers, such as zirconia or titania, may be used incombination with silica and/or alumina fibers in the matrix.

The nature of the fused-fiber matrix network will be seen below withrespect to FIGS. 2A-2D. The matrix density of between 3.5 and 5.5pounds/ft³ refers to the density of the matrix in fused form. The freevolume of the matrix refers to the void volume of the matrix asmeasured, for example, by the volume of water that can be taken up by aft³ of the matrix. To illustrate, a free volume of 90 percent means thatthe total volume occupied by the matrix fibers is 10% and the totalvolume that could be occupied by a liquid is 90%.

The matrix in FIG. 1A, indicated at 20, is formed of a fused-fiber block22 containing an array 24 of tubular channels, such as channels 26,extending through the block. The array alloys fluid circulation ininterior regions of the block, as will be described below.

The matrix in FIG. 1B, indicated at 27, is formed of a series of thinplates, such as plates 28, having the fused-fiber matrix construction ofthe invention. The plates have a preferred thickness between about 1 to5 mm or greater, with a comparable spacing between the plates. A base 29in the matrix used to support the plates as indicated.

FIGS. 2A-2D are scanning electron microscopy (SEM) photomicrographs of afused-fiber matrix composed of about 80 percent of fiber weight ofsilica fibers and 20 percent by fiber weight of alumina fibers, taken at200× (2A), 1,000× (2B), 2,000× (2C), and 7,000× (2D) magnification. Theportion of the matrix shown in FIG. 2A, shows a "nest" of fused silicaand alumina fibers, such as fibers 30, ranging in size from about 200 μmto 10 mm in length. The higher magnification SEM micrograph seen in FIG.2B shows how the fibers are fused at their points of intersection toform a rigid fiber structure having 3-dimensionally continuous networkof interconnecting voids or pores, such as voids 31, which tend to have"long" (uninterrupted) dimensions between about 10-100 μm. That is, thefused fibers are substantially randomly oriented, forming in alldirections, interconnecting voids defined by groups of fused fibers.

The 2,000× magnification micrograph (FIG. 2C) clearly shows both silicafibers, such as fibers 32, which are smooth surfaced, and aluminafibers, such as fibers 34. The silica fibers have diameterspredominantly in the 1.0-1.3 μm size range, and the alumina fibers, inthe 2.5-3.5 μm size range. The mottled regions on the alumina fibers,such as region 36 in fiber 34, presumably represent grain growth thatoccurs during the high-temperature sintering step used in forming thematrix. Clearly visible in FIG. 2C are fusion junctions between twosilica fibers, such as junction 38 between silica fibers 32, 40; fusionjunctions between silica and alumina fibers, such as junction 44 betweensilica fiber 32 and alumina fiber 34; and fusion junctions between twoalumina fibers, such as junction 46 between alumina fibers 34, 48.

The junction region 46 at the lower center in FIG. 2C is shown at 7,000×magnification in FIG. 2D. The micrograph shows more clearly the texturedgrain-growth regions of the alumina fibers, and both silica/alumina andalumina/alumina fiber junctions.

In the embodiments shown in FIGS. 1A and 1B, the density of the matrixis uniform in each block or plate dimension. In a second generalembodiment of the matrix, which is shown end-on at 50 in FIG. 3A, thematrix has a fiber density gradient progressing in the bottom-to-topdirection. In a typical matrix, the gradient varies between a selecteddensity in the range between 3.5-5.0 pounds/ft³ in an "upper" matrixregion 50a, to a selected density in the range between about 5.5 to 12pounds/ft³ in an opposite matrix region 50b.

In another embodiment, the matrix has a discontinuous gradient ofdensity, fiber sizes, and/or fiber composition. The embodimentillustrated end-on at 52 in FIG. 3B is formed of three stacked layers52a-52c, each having a different fiber diameter. For example, the lowerplate is formed of fused silica fibers having fiber diameters of aselected size in the size range between 1-3 μm; the middle layer, silicafibers of a selected size in the diameter size range between 3-5 μm; andthe upper layer, silica fibers of a selected size in the size rangebetween 5-20 μm.

In the matrix just described, larger-diameter fibers are associated withlarger void or pore sizes in the matrix due to the different packingdensities of the fiber at a given fiber-weight density. The dependenceof pore or void size on fiber diameter is demonstrated by the mercuryporosimetry study on matrices formed in accordance with the invention,with different fiber sizes.

In this study, the percent intrusion of mercury into a matrix, as afunction of mercury intrusion pressure, was measured using aMicromeretics PoreSizer 9320 mercury porosimeter. Sample sizes withdimensions of 0.5625 inch diameter by 0.4 inch height were cored from afused matrix block formed in accordance with the invention. Theintrusion pressure was varied from 0.4 to 30 psi. FIG. 4 shows theobserved intrusion vs psi curves, over the pressure range 0.4 to 4 psi,for matrices formed from silica fibers having diameters of 1.3 μm(dash-dot line), a mixture of 1.3 and 3 μm (dash line), 3 μm (dottedline), and 6 μm (dash-dot-dot line).

As seen, the percent intrusion is significantly higher, for a givenintrusion pressure between 0.4 and 4 psi, for larger-diameter fibers,indicating that a matrix formed of such fibers has significantly largerpores or voids.

The discontinuous matrix shown in FIG. 3B may alternatively be formed ofdiscontinuous plates having different fiber compositions, e.g.,different silica/alumina weight ratios, or different fiber densities, orcombinations of different fiber diameters, composition and density.

FIGS. 5A and 5B are scanning electron micrographs of a region ofdiscontinuous, layered matrix 57 having different fiber-density layers,here showing a relatively low-density fiber layer 58 at the interfacewith a relatively high-density fiber layer 59, taken at 110× (FIG. 5A)and 500× (FIG. 5B) magnification. The figure shows the larger pore orvoid sizes in the lower-density layer, and also the fused-fiberconnections at the layer interface.

II. Preparing the Matrix

This section describes the preparation of the matrix described inSection I, in accordance with another aspect of the invention. Ingeneral, the method includes forming a fiber slurry having desiredviscosity and fiber dispersion characteristics, allowing the slurry tosettle under conditions that produce a selected fiber density andorientation, drying the resulting fiber block, and sintering the blockto form the desired fused-fiber matrix.

A. Fiber Treatment

The silica (SiO₂) and/or alumina (Al₂ O₃) fibers used in preparing thematrix are available from a number of commercial sources, in selecteddiameters (fiber thicknesses) between about 0.5 μm-20 μm. A preferredsilica fiber is a high purity, amorphous silica fiber (99.7% pure), suchas fabricated by Manville Corporation (Denver, Colo.) and sold under thefiber designation of "Q-fiber". High purity alumina fibers (average 3microns) may be procured, for example, from ICI Americas, Inc.(Wilmington, Del.).

In a preferred heat treatment, the silica fibers are compressed intopanels, e.g., using a Torit Exhaust System and compaction unit. Thecompressed panels are sent passed through a furnace, e.g., a HarperFuzzbelt furnace or equivalent at 2200° F. for 120 minutes,corresponding to a speed setting of about 2.7 inches/minute. The heattreatment is used to close up surface imperfections on the fibersurfaces, making the matrix more stable to thermal changes on sintering.The heat treatment also improves fiber chopping properties, reducingfabrication time.

In a preferred method, the heat-treated fibers are washed to removedebris and loose particles formed during fiber manufacturing.

B. Preparing a Fiber Slurry

Silica and/or alumina fibers from above are blended to form a fiberslurry that is used in forming a "green-state" block that can besintered to form the desired matrix.

The slurry is formed to contain, in an aqueous medium, silica, alumina,or silica and alumina fibers of the type described above, at afiber:liquid weight ratio of between about 1:25 to 1:70, where theliquid weight refers to the liquid weight of the final slurrypreparation.

The slurry preferably includes a thickening agent effective to give theslurry a viscosity between about 1,000 and 25,000 centipoise, asmeasured by standard methods (ref). The viscosity agent may be any of anumber of well-known hydrophilic polymers, such as polyvinylalcohol,polyvinylacetate, polyvinylpyrrolidone, polyurethane, polyacrylamide,food thickeners, such as gum arabic, acacia, and guar gum, andmethacrylate type polymers. The polymers preferably have molecularweights greater than about 25-50 Kdaltons, and are effective to increasesolution viscosity significantly at concentrations typically betweenabout 0.5-10 weight percent solution.

Preferred thickening agents polymers that also have tacky or adhesiveproperties, such as methyl cellulose, terpolymers of maleic anhydride,alkyl vinyl ether, and an olefin (U.S. Pat. No. 5,034486), copolymers ofethylene and olefins (U.S. Pat. No. 4,840,739), cellulose-containingpastes (U.S. Pat. No. 4,764,548), and soy polysaccharides. One preferredthickening agent is methylcellulose, e.g., the polymer sold under thetradename Methocel A4M and available from Dow Chemical Co. (Midland,Mich.).

Where the matrix is formed of high-purity silica fibers and/or alumina,the slurry is also formed to contain a source of boron that functions,during sintering, to form a boron/silica or boron/alumina surfaceeutectic that acts to lower the melting temperature of the fibers, attheir surfaces, to promote fiber/fiber fusion at the fiberintersections. In a preferred embodiment, the boron is supplied in theslurry as boron nitride particles 15 to 60 μm in size particles. Suchparticles can be obtained from Carborundum (Amherst, N.Y.). The amountof boron nitride is preferably present in the slurry in an amountconstituting between about 2-12 weight percent of the total fiberweight.

The adhesive property of the thickening agent described above is usefulin adhering particles of boron nitride and, if used, silicon carbide, tothe fibers in the slurry, to produce a relatively uniform of particlesin the slurry, and prevent the particles from settling out of slurryduring the molding process described below.

This is illustrated in FIG. 6, which shows a scanning electronmicrograph of a portion of a dried fiber block 60 of silica and/oralumina fibers 64 with boron nitride particles, such as particle 66,distributed over the fibers. The even distribution of particlesthroughout the block is advantageous in achieving effective andrelatively uniform boron concentrations throughout the matrix duringsintering, as described below.

The slurry preferably also contains a dispersant which acts to coat thefibers and help disperse the fibers, both to increase slurry viscosity,and to prevent silica fibers from "bundling" and settling out of theslurry as fiber aggregates during the molding process described below.The dispersant is preferably one which imparts a significant chargeand/or hydrophilicity to the fibers, to keep the fibers separated duringslurry formation and settling during the molding process.

For use with silica fibers, ammonium salts are particularly useful asdispersants, because the ammonium cation is released from the matrix inthe form of ammonia during matrix drying and/or sintering. Preferredammonium salts are the salts of polyanionic polymers, such as ammoniumpolymethylmethacrylate, or the ammonium salt of other carboxylatedpolymers. One preferred dispersant agent is the ammoniumpolymethylmethacrylate polymer sold by R. T. Vanderbilt under thetradename Darvan 821A. The polymer dispersant is preferably added to theslurry to make up between about 0.2 to 5 percent of the total liquidvolume of the slurry.

The slurry may further contain between about 1-5 percent by weightsilicon carbide particles, such as obtainable from Washington MillsElectro Minerals Corp. (Niagara Fall, N.Y.).

A preferred method for preparing a slurry of the type just described isdetailed in Example 1. Briefly, heat-treated silica fibers are suspendedin water at a preferred fiber:water ratio of about 1:300 to 1:800. Thefiber slurry is pumped through a centrifugal cyclone to remove shotglass and other contaminants, such as high soda particles. The fibercake formed by centrifugation is cut into segments, dried at 550° F. forat least 8 hours, and then broken into smaller chunks for forming thematrix.

Fragments of the silica fiber cake are mixed in a desired weight ratiowith alumina fibers, and the fibers are dispersed in an aqueous solutioncontaining the dispersing agent. At this point, the fibers arepreferably chopped to a desired average fiber length in alow-shear/high-shear mixer. In general, the greater the degree ofchopping, the shorter the fibers, producing better packing and a lessopen matrix structure. Similarly, longer fibers lead to more open matrixstructure. The fiber mixing is preferably carried out under condition toproduce average fiber sizes of a selected size in the 1-10 mmfiber-length range.

After mixing, the fibers are allowed to settle, and the liquid/fiberratio is reduced by decanting off some of the dispersing liquid. To thisslurry is added an aqueous gel mixture formed of the viscosity agent,e.g., methyl cellulose, and the matrix particles, e.g., boron nitrideparticles, and the slurry components are mixed to form the desiredhigh-viscosity slurry. The slurry is now ready to be transferred to acasting mold, to prepare the green-state block, as described in the nextsection.

C. Forming a Dried Fiber Block

The method of forming a green-state block, i.e., a dried, rigid matrixof unfused fibers, from the above fiber slurry, is illustrated in FIGS.7A-7C. According to an important aspect of the method, the slurry isallowed to settle and is dewatered in a fashion designed to achieve arelatively uniform fiber density throughout the matrix, and relativelyrandomly oriented fibers, i.e., with little a fiber orientationpreference in the direction of settling.

In the first step, illustrated in FIG. 7A, a slurry 65 is added to amold 66 equipped with a lower screen 68 sized to retain slurry fibers.For fiber sizes in the range 1-10 mm, the screen has a mesh size betweenabout 8 to 20 squares/inch. The mold has a lower collection trough 70equipped with a drain 72 and a vacuum port 74 connected to a suitablevacuum source.

Initially, the slurry is added to the mold and, after stirring theslurry to release gas bubbles, is allowed to settled under gravity,until the level of water in the mold, indicated at 76 is about 1-2inches above the level of the desired final compaction height, i.e., thefinal height of the dewatered block. For a slurry of about 12 1 added toa 18 cm² square mold, the initial settling takes about 3-10 minutes.

The partially drained slurry in the mold is now compacted with acompacting ram 78 to force additional water from slurry. This is done byallowing the ram to act against the upper surface of the slurry underthe force of gravity, while draining the water forced through screen 68from the mold. Water is squeezed from the slurry until the ram reachesthe desired compaction height, as shown in FIG. 7B. With the slurryvolume and mold dimensions just given, a ram having a weight of about 7lbs is effective to compress the partially dewatered slurry in a periodof about 0.2 to 2 minutes.

In the final step of compacting and dewatering, the drain is closed andvacuum is applied to port 74 until the block is completely dewatered. Avacuum of between about 0.01 to 0.5 atm is effective to produce completedewatering of the mold in a period of about 0.2 to 5 minutes. As seen inFIG. 3C, the vacuum dewatering may result in the upper surface of theblock pulling away from the ram.

The dewatered block is now removed from the mold and dried in an oven,typically at a temperature between 250°-500° F. In the dried matrix, theviscosity agent, and to a lesser extent, the dispersant agent, act tobond the fibers at their intersections, forming a rigid, non-fusedblock. The target density of the matrix after drying is between about3.3 to 5.3 pounds/ft³. Details of the molding and drying steps, asapplied to producing one exemplary silica/alumina fiber matrix, aregiven in Example 2, Parts A and B.

The green-state matrix may be formed to include sacrificial fillerelement(s) that will be vaporized during sintering, leaving desiredvoids in the final fused matrix block. The filler elements arepreferably formed of polymer or graphite. As one example, 1A, an arrayof parallel rods (not shown) may be placed in the mold, at the time theslurry is added. Slurry settling and dewatering are as described above,to form the desired green-state block with the included sacrificialelement.

FIG. 8 is a flow diagram of settling and dewatering methods that aresuitable for forming a uniform green-state matrix, according to thesteps just described, or alternatively, for forming a gradient matrixsuch as described above with respect to FIGS. 3A and 3B.

The first step shown is the slurry formation. The slurry may be a singlefiber suspension containing a desired size range and fiber composition.Alternatively, for forming a discontinuous or step fiber matrix, two ormore slurries having different fiber thicknesses, densities, and/orfiber compositions may be formed.

With continued reference to the figure, after the slurry is introducedinto the mold, the steps in settling and dewatering the slurry can bevaried to produce either a continuous gradient of fiber density, asindicated at the left in the figure, or a uniform fiber density, asindicated at the right. The steps in forming a uniform gradient,including an initial settling step, followed by ram compaction and finaldewatering by vacuum have been considered above.

To produce a continuous gradient of fiber densities, the slurry is firstsubjected by dewatering by vacuum, causing material closest to thescreen to be compacted preferentially. When a desired gradient isachieved, the slurry is gravity drained to dewater the slurry, thenram-compacted for further dewatering. The slurry may be subjected to afinal vacuum dewatering, as indicated.

To produce a block having a series of discontinuous layers, each with auniform fiber density, each successive slurry is handled substantiallyas described above for the uniform-density block (at the right in FIG.8). The layers can be formed by successively casting layer upon layer inthe mold, with each successive layer being compacted as described above.Alternatively, a series of block layers, each with a distinctive fibersize/composition and/or density is prepared. Before drying, theindividual blocks are placed together in layers, to form the desireddiscontinuous-layer block. The layers may be "glued" together beforedrying by applying, for example, a layer of boron nitride in theviscosity agent between the layers.

D. Fused Fiber Matrix

In the final step of matrix formation, the green-state block from aboveis sintered under conditions effective to produce surface melting andfiber/fiber fusion at the fiber crossings. The sintering is carried outtypically by placing the green-state block on a prewarmed kiln car. Thematrix is then heated to progressively higher temperature, typicallyreaching at least 2,000° F., and preferably between about 2,200°-2,400°F., until a desired fusion and density are achieved, the target densitybeing between 3.5 and 5.5 pounds/ft³. For a block formed solely ofalumina fibers, a maximum temperature of about 2,350° F. is suitable.One exemplary heating schedule for a silica/alumina matrix is given inExample 2.

In a preferred method, discussed above, the matrix is formed withhigh-purity silica fibers that contain little or no contaminating boronand/or with alumina fibers that are also substantially free of boron. Inorder to achieve fiber softening and fusion above 2,000° F., typicallyin the temperature range 2,000°-2,200° F., it is necessary to introduceboron into the matrix during the sintering process, to form asilica/boron or alumina/boron eutectic mixture at the fiber surface.Boron is preferably introduced, as detailed above, by including boronnitride particles in the green-state block, where the particles areevenly distributed through the block.

During sintering, the boron particles are converted to gaseous N₂ andboron, with the released boron diffusing into the surface of the heatedfibers to produce the desired surface eutectic, and fiber fusion. Thedistribution of boron particles within the heated block ensures arelatively uniform concentration of boron throughout the matrix, andthus uniform fusion properties throughout.

Also during fusion, the viscosity agent and dispersant agents used inpreparing the green-state block are combusted and driven from the block,leaving only the fiber components, and, if added, silicon carbideparticles.

Where the green-state block has been constructed to include asacrificial element, the sintering is also effective to vaporize thiselement, leaving desired voids in the matrix, such as a lattice ofchannels throughout the block.

After formation of the fused-fiber matrix, the matrix block may bemachined to produce the desired shape and configuration. For example,the matrix of FIG. 1A can be formed by drilling an array of channels inthe block; the matrix of FIG. 1B can be formed by cutting the block intothin plates.

III. Polymer Fiber Matrix

In another aspect, the invention includes a fibrous polymer matrix, suchas the matrix 90 shown in FIG. 9A. The matrix is composed of fusedpolymer fibers, and is characterized, in dry form, by: (a) a rigid,three-dimensionally continuous network of open, intercommunicatingvoids, and (b) a free volume of between about 90-98 volume percent. Thatis, the matrix has substantially the same microscopic structureillustrated in FIG. 2A-2D, but where the fibers include polymer fibers,indicated at 91 in FIG. 9B. The fibers may also include up to 80 percentby weight of either silica fibers, alumina fibers, or a combination ofthe two fibers types.

The matrix shown in FIG. 9A is designed for use particularly as asubstrate for cell growth in vitro, and as such, contains an array 92 ofchannels, such as channels 94, extending through the matrix, asdescribed with respect to FIG. 1A. In an alternative embodiment, thematrix has the multi-plate configuration shown for a silica matrix inFIG. 2B.

The fused polymer matrix is formed substantially as described for thesilica, alumina, or silica/alumina fiber matrices described above, butwith the modifications now to be discussed.

The polymer fibers used in constructing the matrix may be anythermoplastic polymers that can be heat fused, typically when heated inthe range 400°-800° F. Exemplary polymer fibers include polyimide,polyurethane, polyethylene, polypropylene, polyether urethane,polyacrylate, polysulfone, polypropylene, polyetheretherketone,polyethyleneterphthalate, polystyrene, and polymer coated carbon fibers.Fibers formed of these polymers, and preferably having thickness in the0.5 to 20 μm range, can be obtained from commercial sources. The fibersmay be chopped, i.e., by shearing, to desired lengths, e.g., in the 0.1to 2 mm range, by subjecting a suspension of the fibers to shear in ahigh-shear blender, as described above.

The polymer fibers may be blended with up to 80 weight percent silicaand/or alumina fibers of the type described above. Preferably, thesilica fibers are heat treated to close up surface imperfections on thefiber surfaces, as described above. The alumina fibers may also be heattreated, e.g., under the sintering conditions described above, toproduce the surface granulation on the fiber seen in FIGS. 2C and 2D.

The aqueous fiber slurry used in preparing the matrix contains, inaddition to fibers, a viscosity agent effective to produce a finalslurry viscosity between about 1,000 and 25,000 centipoise. Viscosityagents of the type mentioned above are suitable. If the polymers fibersare relatively hydrophobic, or if the fibers include silica fibers, theslurry should contain a dispersant effective to prevent the fibers fromaggregating on settling. Such a dispersant may include surfactantsand/or charged polymers, and/or block copolymers, such aspolyethylene/polypropylene block copolymers known to enhance thehydrophilicity of polymer surfaces.

The slurry also contains an adhesive agent effect to retain thegreen-state fiber network in a rigid condition once it is formed. Eitherthe viscosity agent or dispersant may supply the necessary adhesiveproperties. Alternatively, a separate adhesive component may be added tothe slurry.

The above slurry is placed in a settling mold, as above, and the fibersare allowed to settle under dewatering conditions, substantially asdescribed above, to yield randomly oriented fibers having a desiredfiber density. The network is formed into a greenstate block by drying,e.g., at 100°-300° F.

In the final step, the greenstate block is heated under conditions,typically at a temperature between 400°-800° F., effective to producefiber fusion at the fiber points of intersection. The selectedtemperature is near the softening point of the thermoplastic polymer. Atthis temperature, the polymer fibers fuse with one another and withsilica and/or alumina fibers in the block to produce the desired rigid,fused fiber matrix.

IV. Utility: Cell-Growth Substrate

The low-density matrix described above in Sections I-III is designedparticularly for use as a substrate for cell growth in vitro, or in vivoas an implantable substrate.

The architecture of the matrix, and particularly the characteristics ofa rigid, three-dimensionally continuous network of open,intercommunicating voids, and a free volume of between about 90-98volume percent, permit rapid cell growth in three dimensions.

In a preferred embodiment, the matrix is formed of silica fibers,typically in an amount between about 50-100 weight percent of the totalfiber weight. In another preferred embodiment, the matrix is formed toinclude alumina fibers, preferably heated to produce surfacegranulation, in an amount of fiber preferably between about 20-80 weightpercent fiber.

The silica and/or alumina fibers may enhance cell adhesion, and/oradhesion of growth factors, such as fibrofectin, vibronectin, orfibrinogen. Representative cell culture and cell implantationapplications are discussed below.

A. Cell Culture

In one general embodiment, the matrix of the invention is used tosupport cell growth in a cell culture system in vitro. FIGS. 10A-10Cillustrate three cell culture configurations, in accordance with theinvention. The configuration illustrated in FIG. 10A uses a fiber matrix96 of the type shown in FIG. 1A, having a lattice of channels, such aschannels 98, extending through the matrix. The matrix is supported in aculture vessel 100 partially filled with culture medium 102. The mediumis pumped into and through the matrix, as indicated, by a pump 104. Thesystem further includes a filter 106 placed in-line with the pump forextracting desired cell products and/or purifying the medium of cellbi-products. Suitable heating and gas-supply means for maintainingdesired gas and temperature control of the medium may also be employed,as well as means for replenishing the medium. FIG. 10B shows a cellculture configuration which utilizes the a multi-plate matrix, like theone shown in FIG. 1B, and indicated here at 110. As shown, the plates inthe matrix are submerged in a suitable cell culture medium 112 in avessel 114, and the medium is circulated, through the plates by a pump116. The configuration may also include a filter and culture controlmeans, as indicated above.

In a third configuration, shown in FIG. 10C, the matrix is present asfragments, such as fragments 118, which are suspended in a culturemedium 120. The matrix fragments are produced preferably byfragmentizing matrix plates of having a thickness between about 0.2 to 2mm. The matrix fragments, being slightly denser than the culture medium,can be maintained in a suspended state, by gentle stirring or gasbubbling, and can be separated readily from the medium by settling,centrifugation or filtration.

It will be understood that the matrix in the configurations is firststerilized, conventionally, and may be further treated to preabsorbagents which promote cell adhesion to the substrate. Typically theseagents include a divalent cation, such as Mg⁺², and a glycoprotein suchas fibronectin, polyethylene, and/or fibrinogen. The pretreatmentpreferably involves incubating the sterilized matrix in a serum or othermedium containing the growth factors of interest.

Alternatively, the fibers, meaning either silica or polymer fibers, maybe derivatized by covalent attachment of desired growth factors, such asbone osteogenic factor, cytokines, or the like. Methods for derivatizingthe free hydroxyl groups on silica fibers, or free hydroxyl, amine,carboxyl, suldydryl, or aldehyde groups that may be present on polymerfibers are well known.

B. Implantable Cell Matrix

In another general application, the matrix of the invention is used asan implantable substrate for supporting cell growth in vivo. FIG. 11shows, as one example of this application, a hip replacement device 124having a stem 126 designed to be inserted and locked into the femur ofsubject, and a ball 128 which will serve as the ball of the repaired hipjoint. The stem has a titanium inner core 130 which is formed integrallywith the ball. The cover is ensheathed in a fused-fiber matrix 132constructed according to the invention, and which forms a covering overthe core. The matrix covering is preferably formed by machining afused-fiber block of the type described above. The covering may beattached to the stem core by a suitable adhesive, or by heat fusion nearthe melt temperature of the titanium, in the case of a silica and/oralumina fiber matrix.

In operation, the matrix on the stem provides a substrate for the growthand infusion of osteoblast cells, acting to weld the stem to the bonethrough a biological bone structure. The matrix fibers may include bonegrowth factors for promoting bone cell growth into the matrix.

FIG. 12 shows an implantable cell substrate device 131 also constructedaccording to the invention. The device is designed for use as animplantable substrate for supporting growth of a selected tissue cells,such as pancreatic cells or fibroblasts, capable of producing desiredcell metabolites such as insulin or interferon.

The device illustrated has a tubular construction, and provides aspiraled inner core 133 for supporting cell growth, while allowing bodyfluids to bathe the cells, bringing nutrients and removing cellproducts. The device is formed preferably by machining a block offused-fiber matrix of the type disclosed herein. The outer surface ofthe device is coated with a biocompatible material, such as siliconrubber, as indicated at 134 to insulate the fiber matrix from directcontact with the surrounding tissue.

In operation, the device is seeded with the desired cells in culture,preferably until the spiraled core has a maximum cell density. Thedevice is then implanted into a desired tissue region, e.g., anintramuscular site.

The two examples described above illustrate two of a variety of implantdevices, for bone repair, bone replacement, and tissue-cell augmentationor replacement that may be prepared using the cell-substrate matrixmaterial of the invention.

V. Utility: Chromatography

The silica-fiber matrix of the invention is also useful for chemical andcell chromatographic separations.

In one embodiment, the matrix can serve as a substrate for thin-layerchromatographic separations, using well-known solvent-systems anddevelopment conditions. The matrix in this application is preferably athin matrix plate, formed, for example, by slicing a matrix block to adesired thickness, e.g., between 1-3 mm. Alternatively, thin plates maybe prepared by slurry settling, as described above, in thin-plate molds.

In a related aspect, the matrix serves the role of a silica gel columnfor chemical separations by silica gel chromatography. As above, thematrix may be machined from a block matrix mold, or formed by settlingin a suitable cylindrical mold. For both applications, the density ofthe matrix is preferably above the 3.5-5.5 pounds/ft³ matrix densitythat is employed for cell culture.

According to another aspect of the invention, the fused-fiber matrixmaterial having a density between about 3.5 and 5.5 pounds/ft³ is usefulfor cell-separation chromatography, and typically for use in separatingcells and other particles above about 1 micron in size from serumcomponents in a blood sample.

As an example, FIGS. 13A and 13B illustrate a diagnostic test strip 136for use in detecting a serum components, such as glucose, cholesterol,or a cholesterol-containing lipoprotein, such as low density lipoproteinor high-density lipoprotein particles. The strip, which is formed of thefused-silica fiber matrix material of the invention, includes anapplication site 138 at one strip end a detection site 140 at theopposite end. The detection site may include reagents for producing adetectable color signal in the presence of a selected serum analyte.Alternatively, serum from this site may be transferred by physicalcontact to a separate reagent pad.

In operation, a blood sample, e.g., a 25-200 μsample, is added to theapplication site, and the sample is drawn by capillarity toward thestrip's opposite end. Migration of the sample through the interstices ofthe matrix acts to retard the migration rate of larger particles,including blood cells, causing separation of the blood cells separatedinto a slower migrating blood cell fraction 142 and a faster-migratingserum fraction 144, which is received at the detection site free ofblood cells. Analyte detection may occur at this site, as indicated at146, or a separate detection pad may be brought in contact with thestrip site, to draw serum into the pad.

The following examples illustrate methods of preparing silica, aluminaand silica/alumina fused-fiber matrices in accordance with theinvention. The examples are intended to illustrate, but in no way limit,the scope of the invention.

EXAMPLE 1 Forming a Fiber Slurry

A. Fiber Pretreatment

Silica fibers were heat treated as described above. The heat-treatedsilica fibers and/or alumina fibers were dispersed in deionized water ata fiber to deionized water ratio of 1:300 to 800 by weight. The actualdeionized water amount was converted into a volume for ease ofmeasuring. Approximately 150 pounds of fibers was mixed with 900 gallonsof slurry and was pumped through a centrifugal hydrocyclone (BauerBrothers Centrifugal Cleaner) to remove glass shots and other highdensity, high sodium contaminates. The "clean" fiber was collected in acentrifuge, where it was formed into a "cake" and dewatered. The fibercake was then cut into segments. The segments were oven dried at 550° F.for a minimum of 8 hours. Dried segments were broken into smaller chunksand weighed out to the desired amounts for matrix processing.

B. Preparation of Gel Stock

A gel stock was prepared for dispersing the boron nitride and/or siliconcarbide powders into the fiber slurry. A 2 parts by weight methylcellulose (Methocel A4M commercial grade powder from Dow Chemical Co.)was dissolved in 98 parts by weight, of hot deionized water (1 megohm)and vigorously stirred to produce a homogeneous solution. The methylcellulose solution was slowly gelled by placing the mixture container inan ice bath with a maximum temperature of 45° F., for a minimum time of40 minutes. Upon completion of gelling, the solution's viscosity wasmeasured using a Brookfield Synchro-Lectric Viscometer (Model LVT) witha number 1 spindle installed in the instrument. Prior to testing theappropriate sample size was adjusted for temperature to 68°±2° F. whilestirring slowly to avoid air entrapment. Viscosity measurements wererecorded at one spindle speed (0.6 rpm) and expressed in centipoise. Thesolution should have a minimum viscosity of about 4000 centipoise.

C. Preparing a Fiber Suspension

A suspension paste of boron nitride, silicon carbide, and gel stock fromPart B above was prepared by thoroughly mixing the constituentstogether. The weight percentages of the boron nitride was measured frombetween 2 and 12 percent of the total fiber weight. The silicon carbideconcentration was measured from 1 to 5 percent by weight of the totalfiber weight of the matrix. The methyl cellulose (methocel A4M)concentration was determined by the weight of boron nitride to bedispersed. The methyl cellulose to boron nitride ratio can vary frombetween 0.2 to 1.5. The methyl cellulose concentration was measured inweight of gel stock as shown below:

    ______________________________________                                        Gel Stock        60-80%                                                       Boron Nitride.sup.a                                                                            12-35%                                                       Silicon Carbide.sup.b                                                                          5-8%                                                         ______________________________________                                         .sup.a 325 Grit, SHP; Carborundum                                             .sup.b 600 Grit, SIKI I; Washington Mills                                

D. Mixing the Fibers

The silica, alumina, and/or polymer fibers were placed into the mixingcontainer of a variable speed low-shear/high-shear mixer (preferably adouble planetary type mixer). The dispersing agent was prepared bymixing 0.2 to 5% by volume solution of Darvan 821A (ammoniumpolymethylmethacrylate; R. T. Vanderbilt) and deionized water. Adispersing liquid was poured on top of the fibers in a ratio from 25:1to 70:1 parts by weight liquid to fiber. The fibers were mixed into aslurry, and the slurry allowed to settle for an appropriate amount oftime. Then the liquid to fiber ratio was reduced by decanting off someof the dispersing liquid.

The boron nitride, silicon carbide, gel stock suspension was added andblended into the slurry, and the slurry transferred to a casting mold.

EXAMPLE 2 Preparation of Fused-Fiber Matrix

A. Casting the Fiber Slurry

The casting mold used to form the matrix is equipped with a hydraulicbottom, top or combination ram, gravity drain, and vacuum draincapability. Before the fiber slurry was transferred into the castingtower, the tower was rinsed with deionized water. All drain valves werethen closed and deionized water was added to the mold to bring the waterlevel one to two inches above the top of the bottom ram plate. The ramwas actuated to remove any air bubbles from below the ram. The gravitydrain valve was then opened to bring the water level to one-half inchabove the top of the bottom ram plate.

The slurry was transferred to the mold, and stirred slowly with aplastic paddle in circular motions to remove any air bubbles. The toplid was secured and the slurry was gravity drained to remove most of itsliquid. The matrix was then compressed to the desired compressionheight, and vacuum was applied to completely dewater the compressedstructure. The matrix was removed from the mold.

B. Drying the As-Cast Matrix

The as-cast matrix was placed on an Armalon lined baker's type cart, anddried in an electrically heated drying oven at 350° F. for a minimum of16 hours. The target density of the matrix after drying is between 3.3to 5.3 pcf.

C. Fusion of the Matrix

The dried matrix was sintered about 2200° F. using a bottom loadingHarper Elevator Kiln or equivalent; equipped with a programmablecontroller, to achieve fired densities between 3.5 to 5.5 pcf. Kiln carswere pre-warmed to increase temperature uniformity in the kiln andaround the materials being fired. The firing schedule includes thefollowing ramp rates, temperature settings, and estimated soak times.

    ______________________________________                                        Ramp        Temperature                                                                              Soak Time                                              ______________________________________                                        2° F./minute                                                                       1800° F.                                                                          60 minutes                                             2° F./minute                                                                       1900° F.                                                                          6 minutes                                              1° F./minute                                                                       2100° F.                                                                          6 minutes                                              2° F./minute                                                                       2200° F.                                                                          as required to achieve                                                        target density                                         ______________________________________                                    

The kiln was then cooled to 1800° F. prior to removal from the kiln car.

EXAMPLE 3 All Silica Fiber System

225 grams of high purity (99.68+%) heat treated silica fibers (Schuller,108Q fibers, 1.2 um to 1.5 um in diameter) were dispersed in 12 litersof a 0.4% volumetric solution of Darvan 821A (R. T. Vanderbilt) anddeionized water mixture and mixed for 2 minutes using a low shear doublepropeller mixer. 12.6 grams Boron Nitride Powder (325 mesh, Type SHP,Carborundum) was mixed into 60 grams of a 2% A4M Methocel (Dow Chemical)and deionized water solution.

The boron nitride/Methocel suspension was added to the silica slurry andmixed into the fiber slurry using a low shear double propeller mixer foranother 2 minutes. The slurry was cast in a top open 7"×7" mold with astiff screen bottom. The slurry was allowed to gravity drain at a rateof 0.9 inches/minute. A compression plunger was allowed into the moldwhen the settling slurry reached 2" above the desired block height. Theplunger was stopped to a height of 4.5" from the bottom of the mold, asliquid was still draining from the billet. After nine liters of liquidhad been removed from the cast block, vacuum assisted draining was usedto remove one more liter.

The block, 7"×7"×4.5" in size, was removed from the mold and dried for aminimum of 12 hours at 125° C. The dry density of the block was 4.30 pcf(0.07 g/cc). The block was fired at a ramp rate of 2° C./minute to 1250°C. for 30 minutes. The fired density of the block was 5.32 pcf (0.08g/cc).

EXAMPLE 4

78% Silica Fiber and 22% Alumina Fiber System

176 grams of high purity (99.68+%) heat treated silica fibers (Schuller,108Q fibers, 1.2 um to 1.5 um in diameter) and 49 g of alumina fibers(2.5 to 3.5 microns in diameter, ICI America) were dispersed in 12liters of a 0.4% volumetric solution of Darvan 821A (R. T. Vanderbilt)and deionized water mixture and mixed for 2 minutes using a high shearCowles dissolver mixer at 24,000 rpm. The slurry was allowed to age andsettle for at least 4 hours. Approximately 2 liters of liquid wasremoved from the slurry.

12.6 grams of Boron Nitride Powder (325 mesh, Type SHP, Carborundum) and4.3 grams Silicon Carbide Powder (Washington Mills, 600 Grit, SIKA 1)were mixed into 40 grams of 2% A4M Methocel (Dow Chemical) and deionizedwater solution. The boron nitride/Methocel suspension was added to thesilica/alumina fiber slurry and mixed in using a low shear doublepropeller mixer for 2 minutes. The slurry was cast in a top open 7"×7"mold with a stiff screen bottom. The slurry was allowed to gravity drainat a rate of 0.7 inches/minute. A compression plunger was lowered intothe mold when the settling slurry reached 2 inches above the desiredblock height. The plunger was stopped to a height of 4.75 inches fromthe bottom of the mold, as liquid was still draining from the billet.After several liters of the liquid had been removed from the cast block,vacuum assisted draining was used to remove one more liter.

The block, 7"×7"×4.75" in size, was removed from the mold and dried fora minimum of 12 hours at 125° C. The dry density of the block was 4.30pcf (0.07 g/cc). The block was fired at a ramp rate of 2° C./minute to1250° C. for 45 minutes. The fired density of the block was 4.89 pcf(0.08 g/cc).

EXAMPLE 5 78% Silica Fiber and 22% Alumina Fiber System

176 grams of high purity (99.68%) heat treated silica fibers (Schuller,Code 112Q, 2.51 to 3.81 um in diameter) and 49 grams of alumina fiber(2.5 to 3.5 microns in diameter, ICI America) were dispersed in 12liters of 0.4% volumetric solution of Darvan 821A (R. T. Vanderbilt) anddeionized water mixture and mixed for 1 minute using a high shear Cowlesdissolver mixer at 24,000 rpm. The slurry was allowed to age and settlefor at least 4 hours. Approximately 2 liters of liquid was removed fromthe slurry.

12.6 g Boron Nitride Powder (325 mesh, Type SHP, Carborundum) were mixedinto 40 grams of a 2% ArM Methocel (Dow Chemical)/Deionized watersolution. The boron nitride/Methocel suspension was added to thesilica/alumina fiber slurry and mixed in using a low shear doublepropeller mixer for 2 minutes. The slurry was cast in a top open 7"×7"mold with a stiff screen bottom. The slurry was allowed to gravity drainat a rate of 0.7 inches/minute. A compression plunger was lowered intothe mold when the settling slurry reached 3 inches above the desiredblock height. The plunger was stopped to a height of 5.0 inches from thebottom of the mold, as liquid was still draining from the billet. Afterseveral liters of liquid had been removed from the cast block, vacuumassisted draining was used to remove one more liter. The block,7"×7"×5.0" in size, was removed from the mold and dried for a minimum of12 hours at 125° C. The dry density of the block was 3.71 pcf (0.06g/cc). The block was fired at a ramp rate of 2° C./minute to 1250° C.for 45 minutes. The fired density of the block was 3.85 pcf (0.06 g/cc).

EXAMPLE 6 All Alumina Fiber System

225 grams of alumina fiber (ICI America, 2.5 um to 3.5 um in diameter)were dispersed in 12 liters of a 0.06% volumetric solution of Darvan821A (R. T. Vanderbilt) and deionized water mixture and mixed for 2minutes using a high shear Cowles dissolver mixer. 23 grams BoronNitride Powder (325 mesh, Type SHP, Carborundum) were mixed into 80grams of a 2% A4M Methocel (Dow Chemical)/Deionized water solution. Theboron nitride/Methocel suspension was added to the silica slurry andmixed in using a low shear double propeller mixer for 0.5 minutes. Theslurry was allowed to gravity drain at a rate of 0.5 inches/minute. Acompression plunger was lowered into the mold when the settling slurryreached 2 inches above the desired block height. The plunger was stoppedto a height of 5.0 inches from the bottom of the mold, as liquid wasstill draining from the billet. After nine liters of liquid had beenremoved from the cast block, vacuum assisted draining was used to removeone more liter. The block, 7"×7"×5.0" in size, was removed from the moldand dried for a minimum of 12 hours at 125° C. The dry density of theblock was 4.17 pcf (0.07 g/cc). The block was fired at a ramp rate of 2°C./minute to 1350° C. for 60 minutes. The fired density of the block was4.32 pcf (0.07 g/cc).

While the invention has been described with reference to specificmethods and embodiments, it will be appreciated that variousmodifications and changes may be made without departing from theinvention.

It is claimed:
 1. A porous matrix composed of fused fibers of silica,alumina, or silica and alumina and characterized by:(a) a rigid,three-dimensionally continuous network of open, intercommunicating voidsformed randomly in all directions, (b) a density of between about 3.5and 5.5 pounds/ft3; and (c) a volume occupied by the matrix fibers ofbetween about 2-10 volume percent.
 2. The matrix of claim 1, wherein thematrix is formed of silica fibers having fiber diameters between about0.5 to 20 μm, and fiber lengths between about 1-10 mm.
 3. The matrix ofclaim 1, wherein the matrix is formed of alumina fibers having fiberdiameters between about 1 to 20 μm, and fiber lengths between about 1-10mm.
 4. The matrix of claim 1, wherein the matrix is formed of silica andalumina fibers, and the alumina fibers constitute between about 5-95percent of the total weight of the fibers.
 5. The matrix of claim 1,which further includes between about 1-5 percent by weight siliconcarbide particles.
 6. The matrix of claim 1, which is prepared byheating a fiber block composed of unfused fibers and having a densitybetween about 3.3 and 5.3 pounds/cubic feet, in the presence of boronnitride to a temperature of at least about 2200° F. for a periodsufficient to cause fiber fusion.
 7. The matrix of claim 1 having, inone matrix dimension, a gradient of fiber diameters progressing betweena selected fiber size 1-3 μm in diameter to a selected fiber size 5-20μm in diameter.
 8. The matrix of claim 1 having, in one matrixdimension, a matrix gradient progressing between a selected density3.5-5.0 pounds/ft³ to a selected density 5.5 to 12 pounds/ft³.
 9. Thematrix of claim 1, for use as a support for cells in a culture medium,which further includes a lattice of internal channels formed in thelattice through which liquid medium can be supplied to internal regionsof the matrix.
 10. The matrix of claim 1, for use as a support for cellsin a culture medium, wherein the matrix is composed of a series ofporous-matrix plates separated by voids through which medium can besupplied to plate surfaces.